This randomized, 3-arm, multicentre, phase III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtansine (T-DM1) with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab (Herceptin) plus taxane (docetaxel or paclitaxel) in patients with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer. Patients will be randomized to 1 of 3 treatment arms (Arms A, B or C). Arm A will be open-label, whereas Arms B and C will be blinded.

Progression Free Survival (PFS) based on tumor assessments performed by an Independent Review Facility (IRF) [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

Incidence of adverse events (AEs) [ Time Frame: Up to approximately 78 months after study start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall Survival (OS) truncated at 2 years [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

1-year survival rate [ Time Frame: From baseline to 1 year ] [ Designated as safety issue: No ]

Overall Survival (OS) rate [ Time Frame: Up to approximately 78 months after study start ] [ Designated as safety issue: No ]

Overall or objective response rate [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

Duration of response [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

Time-to-Treatment Failure as assessed by IRF [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

Clinical benefit rate [ Time Frame: Up to approximately 48 months after study start ] [ Designated as safety issue: No ]

75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.

Drug: paclitaxel

80 mg/m2 intravenously weekly for a minimum of 18 weeks

Drug: trastuzumab [Herceptin]

trastuzumab [Herceptin] doses when administered with docetaxel: 8 mg/kg intravenously on cycle 1 followed by 6 mg/kg every 3 weeks in subsequent cycles or trastuzumab (Herceptin) doses when administered with paclitaxel: 4 mg/kg intravenously on day 1 of cycle 1 followed by 2 mg/kg weekly starting on day 8 of cycle 1.

Experimental: Trastuzumab emtansine + pertuzumab

Drug: pertuzumab

840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

Drug: pertuzumab-placebo

840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

Drug: trastuzumab emtansine

3.6 mg/kg intravenously every 3 weeks

Experimental: Trastuzumab emtansine + pertuzumab placebo

Drug: pertuzumab

840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

Drug: pertuzumab-placebo

840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

Drug: trastuzumab emtansine

3.6 mg/kg intravenously every 3 weeks

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Adult patients >/=18 years of age

HER2-positive breast cancer

Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and be a candidate for chemotherapy. Patients with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent.

Patients must have measurable and/or non-measurable disease which must be evaluable per RECIST 1.1

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01120184